Classification of distinct tendinopathy subtypes for precision therapeutics

Chenqi Tang, Zetao Wang, Yuanhao Xie, Yang Fei, Junchao Luo, Canlong Wang, Yue Ying, Peiwen He, Ruojing Yan, Yangwu Chen, Jiayun Huang, Yiwen Xu, Zicheng Wang, Boon Chin Heng, Hengzhi Liu, Jianyou Li, Zi Yin, Haobo Wu, Weishan Chen, Hongwei Ouyang (), Xiao Chen () and Weiliang Shen ()
Additional contact information
Chenqi Tang: Zhejiang University School of Medicine
Zetao Wang: Zhejiang University School of Medicine
Yuanhao Xie: Zhejiang University School of Medicine
Yang Fei: Zhejiang University School of Medicine
Junchao Luo: Zhejiang University School of Medicine
Canlong Wang: Zhejiang University School of Medicine
Yue Ying: Zhejiang University School of Medicine
Peiwen He: Zhejiang University School of Medicine
Ruojing Yan: Zhejiang University
Yangwu Chen: Zhejiang University School of Medicine
Jiayun Huang: Zhejiang University School of Medicine
Yiwen Xu: Zhejiang University School of Medicine
Zicheng Wang: Zhejiang University School of Medicine
Boon Chin Heng: Peking University School and Hospital of Stomatology
Hengzhi Liu: Zhejiang University School of Medicine
Jianyou Li: Zhejiang University School of Medicine
Zi Yin: Zhejiang University
Haobo Wu: Zhejiang University School of Medicine
Weishan Chen: Zhejiang University School of Medicine
Hongwei Ouyang: Zhejiang University
Xiao Chen: Zhejiang University
Weiliang Shen: Zhejiang University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Rotator cuff tendinopathy is the most common tendinopathy type with the worst prognosis. Conventional treatments often elicit heterogeneous drug responses due to the diversity of tendinopathy. Hence, this study attempted a classification of 126 diseased tendons into three distinct subtypes with opposite pathogenic mechanisms based on transcriptomic and clinical features. The hypoxic atrophic subtype with white appearance (Hw) exhibits downregulated neovascularization pathways. The inflammatory proliferative subtype with white appearance (Iw) shows a moderate upregulation of inflammatory characteristics. The inflammatory proliferative subtype with red appearance (Ir) exhibits the highest levels of upregulated neovascularization and inflammatory pathways, along with severe joint dysfunction. We then established research models, including subtype-specific simulations in animal models and clinical data analysis. These revealed that glucocorticoid, a controversial commonly used drug, was only effective in treating the Ir subtype. Hence, the tendinopathy subtypes elucidated in this study have significant implications for developing precision treatment of tendinopathy.

Date: 2024
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DOI: 10.1038/s41467-024-53826-w

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